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Introduction: Recalibration of body ownership perception occurs through an integration among multiple modalities. A recent study has shown that respiratory rhythm also causes the recalibration of ownership perception. However, the risk factors influencing the recalibration of ownership perception caused by vision-respiratory interaction remain unclear. In this study, focusing on aging and Parkinson's disease (PD), we examined the effects of those risk factors on the recalibration. Methods: By applying the rubber hand illusion (RHI), which temporarily alters ownership perception, and using a device that synchronizes the respiratory rhythm with the movement of a mannequin hand, we measured a change in ownership perception in RHI training by vision-respiratory interaction. The changed ownership was compared among the elderly healthy, PD, and young healthy groups. Results: The results showed no difference in the changed ownership between the elderly healthy and PD groups, while the two groups decreased the change in the ownership perception compared to the young healthy group. Discussion: The finding suggests that aging, not PD, related to the recalibration of ownership perception by vision-respiratory interaction. An anomaly in body perception due to aging may be associated with a mechanism in which respiratory rhythm affects the adaptation of body representations. [ABSTRACT FROM AUTHOR]

IntroductionRecalibration of body ownership perception occurs through an integration among multiple modalities. A recent study has shown that respiratory rhythm also causes the recalibration of ownership perception. However, the risk factors influencing the recalibration of ownership perception caused by vision-respiratory interaction remain unclear. In this study, focusing on aging and Parkinson’s disease (PD), we examined the effects of those risk factors on the recalibration.MethodsBy applying the rubber hand illusion (RHI), which temporarily alters ownership perception, and using a device that synchronizes the respiratory rhythm with the movement of a mannequin hand, we measured a change in ownership perception in RHI training by vision-respiratory interaction. The changed ownership was compared among the elderly healthy, PD, and young healthy groups.ResultsThe results showed no difference in the changed ownership between the elderly healthy and PD groups, while the two groups decreased the change in the ownership perception compared to the young healthy group.DiscussionThe finding suggests that aging, not PD, related to the recalibration of ownership perception by vision-respiratory interaction. An anomaly in body perception due to aging may be associated with a mechanism in which respiratory rhythm affects the adaptation of body representations.

The respiratory rhythm is initiated and controlled by the respiratory center. The pre-Bötzinger complex is a key part of the origin of respiratory rhythms in mammals. The regulatory mechanism of the respiratory rhythm has been a prominent topic for researchers. By monitoring the changes in oxygen and carbon dioxide concentrations in the blood, it has been found that peripheral chemoreceptors can significantly influence the respiratory rhythm. In this study, using a closed-loop respiratory control model based on pre-Bötzinger complex neurons, by incorporating the motor pool, lung volume, lung oxygen, blood oxygen, and chemoreceptors, we investigate how the response of the system changes after the same hypoxic perturbation when the initial state of the neuron system is different types of mixed bursting patterns. The results show that the system can recover when the initial state consists of one or two somatic bursters and one dendritic burster. However, the system cannot recover when the initial state consists of three or four somatic bursters and one dendritic burster. Due to the complexity of calcium currents, we simulate the complex calcium current with a square wave current to achieve consistent hypoxic responses in the system. Subsequently, using bifurcation analysis and control theory, we investigate the dynamic mechanisms underlying the changes in the system after hypoxic perturbation. According to the bifurcation analysis, we show that different initial states lead to changes of the bifurcation structure of the system, which result in different responses after hypoxic perturbation. This study contributes to a better understanding of the interaction between the respiratory center and peripheral chemical sensory feedback and their influence on the respiratory rhythm. [ABSTRACT FROM AUTHOR]

This study presents an innovative, non-invasive sleep monitoring system that employs force-sensing resistors (FSRs) embedded in a pillow sheet to analyze sleep quality and detect sleep-related breathing disorders (SDB), offering an alternative to conventional polysomnography (PSG). We employed a comprehensive methodology, integrating FSRs with a wireless network device and dedicated software for real-time, precise data analysis and storage. The FSRs, calibrated to measure biomechanical signals associated with body movement, are integrated with a wireless network device. The experiment involved twenty-seven subjects diagnosed with sleep apnea, and the results were compared with PSG recordings. The intelligent sleep application recorded various sleep metrics, including sleep efficiency (SE), and respiratory rhythm. A regression analysis revealed a strong correlation (R2 = 0.96) between the SE measured by the PSG device and the pillow-sheet sensor systems, confirming the reliability of the latter. The Bland-Altman plot further supported this consistency. In conclusion, the pillow-sheet embedded with FSR sensors is a promising tool for unobtrusive sleep monitoring and SDB detection. It offers comparable accuracy to PSG, with the added benefits of being user-friendly and nonrestrictive, making it suitable for clinical and home settings. The system's ability to provide insights into sleep patterns, detect apnea episodes, and analyze sleep postures presents a significant advancement in sleep research and medicine, with potential applications in personalized sleep health management. [ABSTRACT FROM AUTHOR]

The pre-Bötzinger complex, situated in the ventrolateral medulla, serves as the central generator for the inspiratory phase of the respiratory rhythm. Evidence strongly supports its pivotal role in generating, and, in conjunction with the post-inspiratory complex and the lateral parafacial nucleus, in shaping the respiratory rhythm. While there remains an ongoing debate concerning the mechanisms underlying these nuclei’s ability to generate and modulate breathing, transgenic rodent models have significantly contributed to our understanding of these processes. However, there is a significant knowledge gap regarding the spectrum of transgenic rodent lines developed for studying respiratory rhythm, and the methodologies employed in these models. In this study, we conducted a scoping review to identify commonly used transgenic rodent lines and techniques for studying respiratory rhythm generation and modulation. Following PRISMA guidelines, we identified relevant papers in PubMed and EBSCO on 29 March 2023, and transgenic lines in Mouse Genome Informatics and the International Mouse Phenotyping Consortium. With strict inclusion and exclusion criteria, we identified 80 publications spanning 1997–2022 using 107 rodent lines. Our findings revealed 30 lines focusing on rhythm generation, 61 on modulation, and 16 on both. The primary in vivo method was whole-body plethysmography. The main in vitro method was hypoglossal/phrenic nerve recordings using the en bloc preparation. Additionally, we identified 119 transgenic lines with the potential for investigating the intricate mechanisms underlying respiratory rhythm. Through this review, we provide insights needed to design more effective experiments with transgenic animals to unravel the mechanisms governing respiratory rhythm. The identified transgenic rodent lines and methodological approaches compile current knowledge and guide future research towards filling knowledge gaps in respiratory rhythm generation and modulation.

Aconitine is a sodium channel opener, but its effects on the respiratory center are not well understood. We investigated the dose-dependent effects of aconitine on central respiratory activity in brainstem-spinal cord preparations isolated from newborn rats. Bath application of 0.5–5 μM aconitine caused an increase in respiratory rhythm and decrease in the inspiratory burst amplitude of the fourth cervical ventral root (C4). Separate application of aconitine revealed that medullary neurons were responsible for the respiratory rhythm increase, and neurons in both the medulla and spinal cord were involved in the decrease of C4 amplitude by aconitine. A local anesthetic, lidocaine (100 μM), or a voltage-dependent sodium channel blocker, tetrodotoxin (0.1 μM), partially antagonized the C4 amplitude decrease by aconitine. Tetrodotoxin treatment tentatively decreased the respiratory rhythm, but lidocaine tended to further increase the rhythm. Treatment with 100 μM riluzole or 100 μM flufenamic acid, which are known to inhibit respiratory pacemaker activity, did not reduce the respiratory rhythm enhanced by aconitine + lidocaine. The application of 1 μM aconitine depolarized the preinspiratory, expiratory, and inspiratory motor neurons. The facilitated burst rhythm of inspiratory neurons after aconitine disappeared in a low Ca2+/high Mg2+ synaptic blockade solution. We showed the dose-dependent effects of aconitine on respiratory activity. The antagonists reversed the depressive effects of aconitine in different manners, possibly due to their actions on different sites of sodium channels. The burst-generating pacemaker properties of neurons may not be involved in the generation of the facilitated rhythm after aconitine treatment. [ABSTRACT FROM AUTHOR]

The review addresses an innovative and intensively developing approach to organizing stimulation procedures, closed-loop adaptive neurostimulation, in which sensory stimulation parameters are automatically controlled by feedback signals from the patient's own physiological characteristics. The effects of applying invasive and non-invasive magnetic and electrical brain stimulation techniques, as well as closed-loop acoustic and audiovisual stimulation with a feedback control from human rhythmic processes, are considered. The features and achievements of a new approach to the treatment of various psychosomatic disorders and cognitive rehabilitation therapy are demonstrated on numerous examples. The prospects for the development of these technologies are outlined. The results of the author's own studies in this research trend are presented. [ABSTRACT FROM AUTHOR]

ObjectivesObesity is often associated with glucolipid and/or energy metabolism disorders. Ascophyllum nodosum extract (seaweed extract, SE) and Camellia sinensis-leaf extract (tea extract, TE) have been reported to promote positive metabolic effects through different mechanisms. We investigated the effects of SE and TE on metabolic homeostasis in diet-induced obese mice and discussed their functional characteristics.MethodsMale C57BL/6J mice fed with high-fat diets for 8 weeks were established as obese models and subsequently divided into different intervention groups, followed by SE, TE, and their joint interventions for 10 weeks. Body weight and food intake were monitored. Fasting glucose and oral glucose tolerance tests were interspersed during the experiment. After the intervention, the effects on obesity control were assessed based on body composition, liver pathology section, blood lipids and glucose, respiratory exchange ratio (RER), energy expenditure (EE1, EE2, and EE3), inflammatory factors, lipid anabolism enzymes, and gut flora of the obese mice.ResultsAfter continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower ~4.93 g, vs. HFD 38.02 g), peri-testicular fat masses (lower ~0.61 g, vs. HFD 1.92 g), and perirenal fat masses (lower ~0.21 g, vs. HFD mice 0.70 g). All interventions prevented diet-induced increases in plasma levels of glucose, adiponectin, leptin, and the inflammatory factors IL-1β and TNF-α. The RER was modified by the interventions, while the rhythm of the RER was not. Blood lipids (total cholesterol, triglycerides, and LDL) decreased and were associated with lower lipid anabolism enzymes. In addition, the SE and TE interventions altered the structure and abundance of specific flora. Different interventions inhibited the growth of different genera positively associated with obesity (Escherichia–Shigella, Helicobacter, etc.) and promoted the growth of Akkermansia and Bacteroides, thus affecting the chronic inflammatory state.ConclusionSE and TE both have synergistic effects on weight control and glucolipid metabolism regulation by improving insulin sensitivity and reducing lipid synthesis-related enzyme expression, whereas the combination of SE and TE (3:1) has a better effect on regulating energy metabolism and inhibiting chronic inflammation.

Mammalian respiratory rhythm-generating circuits in the brainstem are subject to neuromodulation by multiple peptidergic afferent inputs controlling circuit behavior and outputs. Although functionally important, actions of neuropeptide modulators have not been fully characterized. We analyzed at cellular and circuit levels two inspiratory patterns intrinsically generated by the preBötzinger complex (preBötC) and their modulation by the neuropeptides bombesin and substance P (SP) in neonatal rat medullary slices in vitro. We found that, in recordings of hypoglossal nerve and preBötC neuron inspiratory activity, some inspiratory bursts occurring spontaneously under basal conditions have a biphasic shape with longer duration than normal inspiratory bursts and occur at a lower frequency. This biphasic burst pattern has been proposed to represent inspiratory activity underling periodic sighs. Bath-applied bombesin or SP decreased the period and increased the duration of both normal inspiratory and biphasic bursts and their underlying synaptic drives. The ratio of the biphasic long-duration burst period to the normal inspiratory burst period and the ratio of their burst durations remained the same before and after peptidergic modulation. Bombesin increased the frequency of the inspiratory rhythm in a Ca2+-independent manner and the frequency of long-duration bursts in a Ca2+-dependent manner. This finding suggests that period and burst duration coupling are due to intrinsic mechanisms controlling simultaneously timing and burst termination within the inspiratory rhythm-generating network. We propose a model in which signaling cascades activated by bombesin and SP modulate mechanisms controlling inspiratory burst frequency and duration to coordinate preBötC circuit behavioral outputs. [ABSTRACT FROM AUTHOR]

Continuous interactions between physiological body–brain rhythms influence how individuals act, perceive, and evaluate their environment. Despite increasing interest, the intricate interface between breathing, cardiac, neural rhythms, and cognitive function remains poorly understood. By evaluating current theoretical and empirical implications, we derive an integrative framework of a 'body–brain dynamic system' that combines a hidden hierarchical structure with dynamical state transitions. We propose that body–brain signals can interchangeably drive state- and task-specific coupling mechanisms which influence cognitive functions. The dynamical nature of this framework parallels the intrinsic variability of human behavior, and ultimately aims at better understanding how individuals act in and adapt to a dynamically changing environment. Although physiological activity from the body and the brain are often studied in isolation, accumulating evidence shows that body signals (e.g., respiratory and heart rhythms) modulate neural activity and influence cognitive functions. We propose to look at continuous and bidirectional body–brain interactions through the lens of a dynamic system, with a hierarchical but flexible functional organization, and the scope to optimize adaptation in a dynamic environment. After defining possible body–brain states in action, re-action, and perception, we provide empirical examples to address the causal role of body–brain dynamics in behavior and put forward implications for its clinical translation. [ABSTRACT FROM AUTHOR]

• Respiratory rhythm as a parameter to measure the health level of animals. • Development a flexible sensors for measuring respiratory rhythms in animals. • Exploring the pattern of change in respiratory rhythms as a function of temperature. • Anticipate the appearance of disease in animals in advance. The health status of livestock will directly or indirectly affect meat quality and farmers' income. Therefore, it is necessary to monitor the physiological indicators of livestock to timely reflect their health status. The respiratory rhythm of animals can provide early warning for the occurrence of diseases, but there is currently limited research on the characteristics of the rhythm. Therefore, this paper conducted the following research. PVDF flexible piezoelectric sensors were prepared by spin-coating, laser-induced graphene, and transfer printing processes, in which three common flexible substrate materials were compared, three key parameters of laser scanning were explored, while practical application tests were carried out on model animals, and the collected respiratory rhythm signals were analyzed in the time and frequency domains. The results showed that (1) posilicone of 25 durometer was identified as the flexible substrate material, and the LIG process with a scanning speed of 120 mm/min, a scanning power of 12 %, and a scanning interval of 0.02 mm as the optimal parameters was determined; (2) the sensor exhibited a response speed of 50 ms, an output voltage of 3.7 v, and still had a stable output; (3) in the monitoring of the respiratory rhythm of rabbits, the monitoring accuracy reached 96.7 %, while the respiratory signal collected by the sensor was randomly intercepted for 10 s, and its respiratory rhythm prediction accuracy reached 95.85 %. At the same time, the abnormal respiratory rhythm change of the animal was found 10 min in advance, giving the farmer more time to deal with the problem. (4) The monitoring of the respiration of farm animals such as Hu sheep is being realised. At the same time, the time domain as well as frequency domain waveforms of the Hu sheep were analysed and compared with the time domain frequency domain plots of the rabbit, which showed that the sensor could achieve good results for both higher frequency breathing and low-frequency breathing. It provides potential technical support for future health monitoring and early prediction of diseases in large farm animals. [ABSTRACT FROM AUTHOR]

This article considers the dynamics of the development of a potential approach to correcting stress-induced states in humans, i.e., adaptive neurostimulation. The approach consists of presenting sensory stimulation automatically modulated by intrinsic rhythmic human processes such as the respiratory rhythm, the heartbeat rhythm, and electroencephalograph (EEG) rhythms. Many examples have shown that real-time self-adjustment of the stimulation parameters by these rhythms leads to a high level personalization of therapeutic stimulation and increases in its efficacy in suppressing stress-induced states. The publications reviewed here point to the advantages of this approach for developing innovatory technologies using complex feedback from endogenous human rhythms to correct a wide spectrum of functional disorders. [ABSTRACT FROM AUTHOR]

The article "How neural networks walk and chew gum" published in the Journal of Physiology explores how the brain's preBötzinger complex generates both regular breathing (eupnoea) and sighs through complex interactions of intrinsic and network properties. Researchers from the College of William and Mary used computational modeling and experimental tests to show how calcium dynamics within the preBötzinger complex lead to the generation of sighs. The study highlights how network properties and intrinsic properties, specifically Ca2+ dynamics, work together to control different aspects of breathing rhythms, shedding light on how single brain networks can perform multiple functions simultaneously. [Extracted from the article]

Neural oscillations can couple networks of brain regions, especially at lower frequencies. The nasal respiratory rhythm, which elicits robust olfactory bulb oscillations, has been linked to episodic memory, locomotion, and exploration, along with widespread oscillatory coherence. The piriform cortex is implicated in propagating the olfactory-bulb-driven respiratory rhythm, but this has not been tested explicitly in the context of both hippocampal theta and nasal respiratory rhythm during exploratory behaviors. We investigated systemwide interactions during foraging behavior, which engages respiratory and theta rhythms. Local field potentials from the olfactory bulb, piriform cortex, dentate gyrus, and CA1 of hippocampus, primary visual cortex, and nasal respiration were recorded simultaneously from male rats. We compared interactions among these areas while rats foraged using either visual or olfactory spatial cues. We found high coherence during foraging compared with home cage activity in two frequency bands that matched slow and fast respiratory rates. Piriform cortex and hippocampus maintained strong coupling at theta frequency during periods of slow respiration, whereas other pairs showed coupling only at the fast respiratory frequency. Directional analysis shows that the modality of spatial cues was matched to larger influences in the network by the respective primary sensory area. Respiratory and theta rhythms also coupled to faster oscillations in primary sensory and hippocampal areas. These data provide the first evidence of widespread interactions among nasal respiration, olfactory bulb, piriform cortex, and hippocampus in awake freely moving rats, and support the piriform cortex as an integrator of respiratory and theta activity. [ABSTRACT FROM AUTHOR]

The neural control of breathing exhibits sex differences. There is now a large effort to account for biological sex in mammalian research, but the degree to which ectothermic vertebrates exhibit sex differences in the central control of breathing is not well-established. Therefore, we compared respiratory-related neural activity in brainstem-spinal cord preparations from female and male bullfrogs to determine if important aspects of the central control of breathing vary with sex. We found that the breathing pattern was similar across males and females, but baseline frequency of the respiratory network was faster in females. The magnitude of the central response to hypercapnia was similar across sexes, but the time to reach maximum burst rate occurred more slowly in females. These results suggest that sex differences may account for variation in traits associated with the control of breathing and that future work should carefully account for sex of the animal in analysis. • Baseline bursting rates were two times greater in females than males. • Males attained maximum response to hypercapnia. • There was no difference between sexes regarding their maximum response to hypercapnia. [ABSTRACT FROM AUTHOR]

Eupnea and gasping in infancy depend on central nervous system (CNS) serotonin (5-hydroxytryptamine; 5-HT). Although previous in vitro preparations have provided some evidence that 5-HT acts through type 2A receptors (5-HT2A) to facilitate eupnea and gasping, here the hypothesis addressed is that 5-HT2A receptor activation is necessary for eupnea and the proper generation of gasping in vivo. To test this, we administered 2,5-dimethoxy-4-iodoamphetamine (DOI; 0.25 mg/kg i.p.), a 5-HT2A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.25 mg/kg i.p.), a 5-HT1A agonist, or vehicle (saline) to 7-9-day-old tryptophan hydroxylase 2 knockout (TPH2-/-) mice. A second experiment assessed the effect of MDL-11,939 (MDL; 10 mg/kg i.p.), the specific 5-HT2A antagonist, or vehicle (DMSO) on the gasping of wild-type (TPH2þ/þ) animals. Drugs were given 15 min prior to five episodes of severe hypoxia that elicited gasping. TPH2-/- breathed more slowly but had the same VE and VE/VO2 compared with TPH2þ/þ. As previously reported, the gasping of TPH2-/- was significantly delayed (P < 0.001) and occurred at a significantly lower frequency compared with TPH2þ/þ (P = 0.04). For both genotypes, DOI hastened eupneic frequency but had no effect on VE or VE/VO2. The gasping of TPH2-/-, although unaffected by 8-OH-DPAT, was indistinguishable from the gasping of TPH2þ/þ following DOI. In TPH2þ/þ, application of MDL led to hypoventilation (P = 0.01), a delay in the appearance of gasping (P = 0.005), and reduced gasp frequency (P = 0.05). These data show that, in vivo, 5-HT2A receptors facilitate both eupnea and gasping. As has been shown in vitro, 5-HT2A probably promotes gasping by exciting hypoxia-resistant pacemaker neurons. [ABSTRACT FROM AUTHOR]

The pre-Bötzinger complex (preBötC), located within the ventral respiratory column, produces inspiratory bursts in varying degrees of synchronization/amplitude. This wide range of population burst patterns reflects the flexibility of the preBötC neurons, which is expressed in variations in the onset/offset times of their activations and their activity during the population bursts, with respiratory neurons exhibiting a large cycle-to-cycle timing jitter both at the population activity onset and at the population activity peak, suggesting that respiratory neurons are stochastically activated before and during the inspiratory bursts. However, it is still unknown whether this stochasticity is maintained while evaluating the coactivity of respiratory neuronal ensembles. Moreover, the preBötC topology also remains unknown. In this study, by simultaneously recording tens of preBötC neurons and using coactivation analysis during the inspiratory periods, we found that the preBötC has a scale-free configuration (mixture of not many highly connected nodes, hubs, with abundant poorly connected elements) exhibiting the rich-club phenomenon (hubs more likely interconnected with each other). PreBötC neurons also produce multineuronal activity patterns (MAPs) that are highly stable and change during the hypoxia-induced reconfiguration. Moreover, preBötC contains a coactivating core network shared by all its MAPs. Finally, we found a distinctive pattern of sequential coactivation of core network neurons at the beginning of the inspiratory periods, indicating that, when evaluated at the multicellular level, the coactivation of respiratory neurons seems not to be stochastic. NEW & NOTEWORTHY By means of multielectrode recordings of preBötC neurons, we evaluated their configuration in normoxia and hypoxia, finding that the preBötC exhibits a scale-free configuration with a rich-club phenomenon. preBötC neurons produce multineuronal activity patterns that are highly stable but change during hypoxia. The preBötC contains a coactivating core network that exhibit a distinctive pattern of coactivation at the beginning of inspirations. These results reveal some network basis of inspiratory rhythm generation and its reconfiguration during hypoxia. [ABSTRACT FROM AUTHOR]

Pulmonary ventilation and respiration are considered to be primarily involved in oxygenation of blood for oxygen delivery to cells throughout the body for metabolic purposes. Other pulmonary physiological observations, such as respiratory sinus arrhythmia, Hering Brewer reflex, cardiorespiratory synchronization, and the heart rate variability (HRV) relationship with breathing rhythm, lack complete explanations of physiological/functional significance. The spectrum of waveforms of breathing activity correlate to anxiety, depression, anger, stress, and other positive and negative emotions. Respiratory pattern has been thought not only to be influenced by emotion but to itself influence emotion in a bi-directional relationship between the body and the mind. In order to show how filling in gaps in understanding could lead to certain future developments in mind–body medicine, biofeedback, and personal health monitoring, we review and discuss empirical work and tracings to express the vital role of bodily rhythms in influencing emotion, autonomic nervous system activity, and even general neural activity. Future developments in measurement and psychophysiological understanding of the pattern of breathing in combination with other parameters such as HRV, cardiorespiratory synchronization, and skin conductivity may allow for biometric monitoring systems to one day accurately predict affective state and even affective disorders such as anxiety. Better affective prediction based on recent research when incorporated into personal health monitoring devices could greatly improve public mental health by providing at-home biofeedback for greater understanding of one’s mental state and for mind–body affective treatments such as breathing exercises.

New Findings: Whatis the topic of this review?This review explores the modulatory role of lung vagal afferents and intra‐neuraxial and carotid body chemoreceptors upon hypoglossal pre‐inspiratory activity.What advances does it highlight?Pre‐inspiratory activity manifesting in hypoglossal neural efferent discharge may be potentiated by mechanical interruption of vagal continuity and challenge with administration of a hypoxic and/or hypercapnic gas mixture and attenuated by static and/or dynamic pulmonary stretch. Differential excitability of, or premotoneuronal volleys exhibiting distinct spatiotemporal patterns of discharge arriving at, motoneurons residing within the hypoglossal motor nucleus may emergently generate phase‐spanning pre‐inspiratory inspiratory activity of hypoglossal neural efferent discharge manifest at the population level. The hypoglossal nerve (XII) innervates muscles mediating excursive movements of the tongue. The population discharge of hypoglossalmotoneuronal axons constituting the hypoglossal nerve precedes and extends through the inspiratory epoch. The epoch subtended between the onsets of hypoglossal and phrenic neural discharge constitutes so‐called pre‐inspiration. Hypoglossal pre‐inspiratory neural discharge serendipitously displaces the tongue along a tensor reducing upper airway resistance anticipative of succeeding inspiratory efforts. Hypoglossal motoneurons exhibiting discharge onset during pre‐inspiration experience successive hyperpolarization of membrane voltage and attenuation of unitary spiking frequency, although a subset may, paradoxically and state‐dependently, exhibit depolarization of membrane voltage and augmentation of neuronal spiking frequency, by dynamic stretch placed upon the alveolar walls and interstitium. Marked static elevation of positive‐end expiratory pressure may induce hypoglossal bursting decoupled from phasic rhythmic phrenic discharge. Augmentation of the amplitude and/or duration of hypoglossal inspiratory discharge during successive pre‐inspiratory and inspiratory epochs by inhalation of a hypoxic and/or hypercapnic gas mixture remains restrained in the presence of intact vagal inputs and is potentiated by interruptions of vagal continuity. Unravelling the mechanisms underlying the genesis of pre‐inspiratory activity will inform our understanding of respiratory rhythm generation and pattern shaping. In the present work, I seek to explore the mechanisms underlying modulation of hypoglossal pre‐inspiratory discharge by hypercapnia, hypoxia and static and dynamic lung stretch placed upon hypoglossal pre‐inspiratory activity, the mechanisms underlying the generation of hypoglossal pre‐inspiratory activity, and the extent of microanatomical and functional overlap between propriobulbar interneuronal microcircuits generating hypoglossal pre‐inspiratory activity and propriobulbar interneuronal microcircuit oscillators generating pre‐inspiratory activity inaugurally inducing respiratory rhythmic activity and thus use experimental data from previous work and that developed by other investigators to explore the modulatory role of lung vagal afferents and intra‐neuraxial and carotid body chemoreceptors upon hypoglossal pre‐inspiratory activity. [ABSTRACT FROM AUTHOR]

Frogs produce two distinct yet highly coordinated ventilatory behaviors, buccal and lung. Lung ventilation occurs in short episodes, interspersed with periods of buccal ventilation. Recent data suggests that two brainstem oscillators are involved in generating these behaviors, one primarily responsible for buccal ventilation, the other for lung. Here we use a modeling approach to demonstrate that the episodic pattern of lung ventilation might be an emergent property of the coupling between the oscillators, and may not require a perturbing input from another, as yet unidentified but previously postulated, neuronal oscillator. © 2004 Elsevier B.V. All rights reserved.

Frogs produce two distinct yet highly coordinated ventilatory behaviors, buccal and lung. Lung ventilation occurs in short episodes, interspersed with periods of buccal ventilation. Recent data suggests that two brainstem oscillators are involved in generating these behaviors, one primarily responsible for buccal ventilation, the other for lung. Here we use a modeling approach to demonstrate that the episodic pattern of lung ventilation might be an emergent property of the coupling between the oscillators, and may not require a perturbing input from another, as yet unidentified but previously postulated, neuronal oscillator. © 2004 Elsevier B.V. All rights reserved.

Infants born prematurely, often associated with maternal infection, frequently exhibit breathing instabilities that require resuscitation. We hypothesized that breathing patterns during the first hour of life would be predictive of survival in an animal model of prematurity. Using plethysmography, we measured breathing patterns during the first hour after birth in mice born at term (Term 19.5), delivered prematurely on gestational day 18.5 following administration of low-dose lipopolysaccharide (LPS; 0.14 mg/kg) to pregnant dams (LPS 18.5), or delivered on gestational day 18.7 or 17.5 by caesarian section (C-S 18.5 and C-S 17.5, respectively). Our experimental approach allowed us to dissociate effects caused by inflammation, from effects due to premature birth in the absence of an inflammatory response. C-S 17.5 mice did not survive, whereas mortality was not increased in C-S 18.5 mice. However, in premature pups born at the same gestational age (day 18.5) in response to maternal LPS injection, mortality was significantly increased. Overall, mice that survived had higher birth weights and showed eupneic or gasping activity that was able to transition to normal breathing. Some mice also exhibited a “saw tooth” breathing pattern that was able to transition into eupnea during the first hour of life. In contrast, mice that did not survive showed distinct, large amplitude, long-lasting breaths that occurred at low frequency and did not transition into eupnea. This breathing pattern was only observed during the first hour of life and was more prevalent in LPS 18.5 and C-S 18.5 mice. Indeed, breath tidal volumes were higher in inflammation-induced premature pups than in pups delivered via C-section at equivalent gestational ages, whereas breathing frequencies were low in both LPS-induced and C-section-induced premature pups. We conclude that a breathing pattern characterized by low frequency and large tidal volume is a predictor for the failure to survive, and that these characteristics are more often seen when prematurity occurs in the context of maternal inflammation. Further insights into the mechanisms that generate these breathing patterns and how they transition to normal breathing may facilitate development of novel strategies to manage premature birth in humans.

In this study, the effect of cardiac resynchronization therapy (CRT) on the relationship between the cardiovascular and respiratory systems in heart failure subjects was examined for the first time. We hypothesized that alterations in cardio-respiratory interactions, after CRT implantation, quantified by signal complexity, could be a marker of a favorable CRT response. Sample entropy and scaling exponents were calculated from synchronously recorded cardiac and respiratory signals 20 min in duration, collected in 47 heart failure patients at rest, before and 9 months after CRT implantation. Further, cross-sample entropy between these signals was calculated. After CRT, all patients had lower heart rate and CRT responders had reduced breathing frequency. Results revealed that higher cardiac rhythm complexity in CRT non-responders was associated with weak correlations of cardiac rhythm at baseline measurement over long scales and over short scales at follow-up recording. Unlike CRT responders, in non-responders, a significant difference in respiratory rhythm complexity between measurements could be consequence of divergent changes in correlation properties of the respiratory signal over short and long scales. Asynchrony between cardiac and respiratory rhythm increased significantly in CRT non-responders during follow-up. Quantification of complexity and synchrony between cardiac and respiratory signals shows significant associations between CRT success and stability of cardio-respiratory coupling.

Infants born prematurely, often associated with maternal infection, frequently exhibit breathing instabilities that require resuscitation. We hypothesized that breathing patterns during the first hour of life would be predictive of survival in an animal model of prematurity. Using plethysmography, we measured breathing patterns during the first hour after birth in mice born at term (Term 19.5), delivered prematurely on gestational day 18.5 following administration of low-dose lipopolysaccharide (LPS; 0.14 mg/kg) to pregnant dams (LPS 18.5), or delivered on gestational day 18.7 or 17.5 by caesarian section (C-S 18.5 and C-S 17.5, respectively). Our experimental approach allowed us to dissociate effects caused by inflammation, from effects due to premature birth in the absence of an inflammatory response. C-S 17.5 mice did not survive, whereas mortality was not increased in C-S 18.5 mice. However, in premature pups born at the same gestational age (day 18.5) in response to maternal LPS injection, mortality was significantly increased. Overall, mice that survived had higher birth weights and showed eupneic or gasping activity that was able to transition to normal breathing. Some mice also exhibited a "saw tooth" breathing pattern that was able to transition into eupnea during the first hour of life. In contrast, mice that did not survive showed distinct, large amplitude, long-lasting breaths that occurred at low frequency and did not transition into eupnea. This breathing pattern was only observed during the first hour of life and was more prevalent in LPS 18.5 and C-S 18.5 mice. Indeed, breath tidal volumes were higher in inflammation-induced premature pups than in pups delivered via C-section at equivalent gestational ages, whereas breathing frequencies were low in both LPS-induced and C-section-induced premature pups. We conclude that a breathing pattern characterized by low frequency and large tidal volume is a predictor for the failure to survive, and that these characteristics are more often seen when prematurity occurs in the context of maternal inflammation. Further insights into the mechanisms that generate these breathing patterns and how they transition to normal breathing may facilitate development of novel strategies to manage premature birth in humans. [ABSTRACT FROM AUTHOR]

The mammalian olfactory bulb displays a prominent respiratory rhythm, which is linked to the sniff cycle and is driven by sensory input from olfactory receptors in the nasal sensory epithelium. In rats and mice, respiratory frequencies occupy the same band as the hippocampal θ-rhythm, which has been shown to be a key player in memory processes. Hippocampal and olfactory bulb rhythms were previously found to be uncorrelated except in specific odor-contingency learning circumstances. However, many recent electrophysiological studies in both rodents and humans reveal a surprising cycle-by-cycle influence of nasal respiration on neuronal activity throughout much of the cerebral cortex beyond the olfactory system, including the prefrontal cortex, hippocampus, and subcortical structures. In addition, respiratory phase has been shown to influence higher-frequency oscillations associated with cognitive functions, including attention and memory, such as the power of γ-rhythms and the timing of hippocampal sharp wave ripples. These new findings support respiration's role in cognitive function, which is supported by studies in human subjects, in which nasal respiration has been linked to memory processes. Here, we review recent reports from human and rodent experiments that link respiration to the modulation of memory function and the neurophysiological processes involved in memory in rodents and humans. We argue that respiratory influence on the neuronal activity of two key memory structures, the hippocampus and prefrontal cortex, provides a potential neuronal mechanism behind respiratory modulation of memory. [ABSTRACT FROM AUTHOR]

Highlights • The in situ perfused brainstem preparation of guinea pig generates physiological cardio-respiratory activity patterns. • It preserves central network activity required for multi-synaptic sensory reflex integration. • First demonstration that mechanical stimulation of the trachea triggers an in situ expiration reflex. • This new method will help to advance the field of central control of airway defense. Abstract The perfused working heart brainstem preparation of rodents has become a widely used tool to study brainstem function. Here, we adapt this experimental technique for newborn guinea pigs (postnatal day 7–14) to develop a tool that enables investigation of airway defense mechanisms not observed in other rodents. The perfused guinea pig brainstem preparation generates a stable eupnea-like motor pattern recorded from the phrenic, recurrent laryngeal and intercostal nerves and basic cardio-respiratory reflexes, including the arterial chemoreceptor, the baroreceptor reflex. In addition a fictive laryngeal cough reflex can be reliably elicited after mechanical stimulation of the trachea. Single unit recordings within the ponto-medullary respiratory column show robust central respiratory neuronal activity. Additionally, as in other species ponto-medullary transection of the brainstem produces apneusis. The latter suggests that the preparation fully preserves ponto-medullary synaptic connectivity that is required for eupnea-like respiratory rhythm and pattern formation and the mediation of various cardio-respiratory reflexes. We conclude that this novel research tool provides an alternative to established rat and mouse preparations and may become a experimental tool for the investigation of central mechanisms that mediate laryngeal cough. [ABSTRACT FROM AUTHOR]

Research on respiratory sinus arrhythmia, or high-frequency heart rate variability (its frequency-domain equivalent), has been popular in psychology and the behavioral sciences for some time. It is typically interpreted as an indicator of cardiac vagal activity. However, as research has shown for decades, the respiratory pattern can influence the amplitude of these noninvasive measures substantially, without necessarily reflecting changes in tonic cardiac vagal activity. Although changes in respiration are systematically associated with experiential and behavioral states, this potential confound in the interpretation of RSA, or HF-HRV, is rarely considered. Interpretations of within-individual changes in these parameters are therefore only conclusive if undertaken relative to the breathing pattern. The interpretation of absolute levels of these parameters between individuals is additionally burdened with the problem of residual inspiratory cardiac vagal activity in humans. Furthermore, multiple demographic, anthropometric, life-style, health, and medication variables can act as relevant third variables that might explain associations of RSA or HF-HRV with experiential and behavioral variables. Because vagal activity measured by these parameters only represents the portion of cardiac vagal outflow that is modulated by the respiratory rhythm, alternative interpretations beyond cardiac vagal activity should be considered. Accumulating research shows that activity of multiple populations of neurons in the brain and the periphery, and with that organ activity and function, are modulated rhythmically by respiratory activity. Thus, observable health benefits ascribed to the cardiac vagal system through RSA or HF-HRV may actually reflect beneficial effects of respiratory modulation. Respiratory rhythmicity may ultimately provide the mechanism that integrates central, autonomic, and visceral activities. • Respiration rate and volume alter RSA amplitude independent of, in the absence of, changes in cardiac vagal tone. • Respiration is sensitive to a host of psychological processes. • Absolute RSA levels are imperfect measures of individual vagal tone differences. • Respiration entrains many physiological processes and could be an indicator of health. • Respiration acts as a powerful neurovisceral integrator. [ABSTRACT FROM AUTHOR]

It is known that in pathological conditions, physiological systems develop changes in the multiscale properties of physiological signals. However, in real life, little is known about how changes in the function of one of the two coupled physiological systems induce changes in function of the other one, especially on their multiscale behavior. Hence, in this work we aimed to examine the complexity of cardio-respiratory coupled systems control using multiscale entropy (MSE) analysis of cardiac intervals MSE (RR), respiratory time series MSE (Resp), and synchrony of these rhythms by cross multiscale entropy (CMSE) analysis, in the heart failure (HF) patients and healthy subjects. We analyzed 20 min of synchronously recorded RR intervals and respiratory signal during relaxation in the supine position in 42 heart failure patients and 14 control healthy subjects. Heart failure group was divided into three subgroups, according to the RR interval time series characteristics (atrial fibrillation (HFAF), sinus rhythm (HFSin), and sinus rhythm with ventricular extrasystoles (HFVES)). Compared with healthy control subjects, alterations in respiratory signal properties were observed in patients from the HFSin and HFVES groups. Further, mean MSE curves of RR intervals and respiratory signal were not statistically different only in the HFSin group (p = 0.43). The level of synchrony between these time series was significantly higher in HFSin and HFVES patients than in control subjects and HFAF patients (p < 0.01). In conclusion, depending on the specific pathologies, primary alterations in the regularity of cardiac rhythm resulted in changes in the regularity of the respiratory rhythm, as well as in the level of their asynchrony.

The orbitofrontal cortex (OFC) has been implicated in a multiplicity of complex brain functions, including representations of expected outcome properties, post-decision confidence, momentary food-reward values, complex flavors and odors. As breathing rhythm has an influence on odor processing at primary olfactory areas, we tested the hypothesis that it may also influence neuronal activity in the OFC, a prefrontal area involved also in higher order processing of odors. We recorded spike timing of orbitofrontal neurons as well as local field potentials (LFPs) in awake, head-fixed mice, together with the breathing rhythm. We observed that a large majority of orbitofrontal neurons showed robust phase-coupling to breathing during immobility and running. The phase coupling of action potentials to breathing was significantly stronger in orbitofrontal neurons compared to cells in the medial prefrontal cortex. The characteristic synchronization of orbitofrontal neurons with breathing might provide a temporal framework for multi-variable processing of olfactory, gustatory and reward-value relationships.

Rhythmic eupneic breathing in mammals depends on the coordinated activities of the neural system that sends cranial and spinal motor outputs to respiratory muscles. These outputs modulate lung ventilation and adjust respiratory airflow, which depends on the upper airway patency and ventilatory musculature. Anesthetics are widely used in clinical practice worldwide. In addition to clinically necessary pharmacological effects, respiratory depression is a critical side effect induced by most general anesthetics. Therefore, understanding how general anesthetics modulate the respiratory system is important for the development of safer general anesthetics. Currently used volatile anesthetics and most intravenous anesthetics induce inhibitory effects on respiratory outputs. Various general anesthetics produce differential effects on respiratory characteristics, including the respiratory rate, tidal volume, airway resistance, and ventilatory response. At the cellular and molecular levels, the mechanisms underlying anesthetic-induced breathing depression mainly include modulation of synaptic transmission of ligand-gated ionotropic receptors ( e.g. , γ-aminobutyric acid, N-methyl-D-aspartate, and nicotinic acetylcholine receptors) and ion channels ( e.g. , voltage-gated sodium, calcium, and potassium channels, two-pore domain potassium channels, and sodium leak channels), which affect neuronal firing in brainstem respiratory and peripheral chemoreceptor areas. The present review comprehensively summarizes the modulation of the respiratory system by clinically used general anesthetics, including the effects at the molecular, cellular, anatomic, and behavioral levels. Specifically, analgesics, such as opioids, which cause respiratory depression and the "opioid crisis", are discussed. Finally, underlying strategies of respiratory stimulation that target general anesthetics and/or analgesics are summarized., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Highlights • Glutamatergic drive to the preBötzinger Complex is essential for respiratory rhythm. • Glutamatergic drive to the Bötzinger Complex contributes to respiratory phase timing. • Inspiratory premotor neurons receive continuous tonic excitatory inputs. • Bötzinger Complex neurons inhibit inspiratory premotor neurons during expiration. Abstract Glutamate is the predominant excitatory neurotransmitter in the ventral respiratory column; however, the contribution of glutamatergic excitation in the individual subregions to respiratory rhythm generation has not been fully delineated. In an adult, in vivo, decerebrate rabbit model during conditions of mild hyperoxic hypercapnia we blocked glutamatergic excitation using the receptor antagonists 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) and d(–)-2-amino-5-phosphonopentanoic acid (AP5). Disfacilitation of the preBötzinger Complex caused a decrease in inspiratory and expiratory duration as well as peak phrenic amplitude and ultimately apnea. Disfacilitation of the Bötzinger Complex caused a decrease in inspiratory and expiratory duration; subsequent disfacilitation of the preBötzinger Complex resulted in complete loss of the respiratory pattern but maintained tonic inspiratory activity. We conclude that glutamatergic drive to the preBötzinger Complex is essential for respiratory rhythm generation. Glutamatergic drive to the Bötzinger Complex significantly affects inspiratory and expiratory phase duration. Bötzinger Complex neurons are responsible for maintaining the silent expiratory phase of the phrenic neurogram. [ABSTRACT FROM AUTHOR]

An important unresolved question about neural processing is the mechanism by which distant brain areas coordinate their activities and relate their local processing to global neural events. A potential candidate for the local-global integration are slow rhythms such as respiration. In this study, we asked if there are modulations of local cortical processing that are phase-locked to (peripheral) sensory-motor exploratory rhythms. We studied rats on an elevated platform where they would spontaneously display exploratory and rest behaviors. Concurrent with behavior, we monitored whisking through electromyography and the respiratory rhythm from the olfactory bulb (OB) local field potential (LFP). We also recorded LFPs from dorsal hippocampus, primary motor cortex, primary somatosensory cortex, and primary visual cortex. We defined exploration as simultaneous whisking and sniffing above 5 Hz and found that this activity peaked at ~8 Hz. We considered rest as the absence of whisking and sniffing, and in this case, respiration occurred at ~3 Hz. We found a consistent shift across all areas toward these rhythm peaks accompanying behavioral changes. We also found, across areas, that LFP gamma (70-100 Hz) amplitude could phase-lock to the animal's OB respiratory rhythm, a finding indicative of respiration-locked changes in local processing. In a subset of animals, we also recorded the hippocampal theta activity and found that occurred at frequencies overlapped with respiration but was not spectrally coherent with it, suggesting a different oscillator. Our results are consistent with the notion of respiration as a binder or integrator of activity between brain regions. [ABSTRACT FROM AUTHOR]

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The orbitofrontal cortex (OFC) has been implicated in a multiplicity of complex brain functions, including representations of expected outcome properties, post-decision confidence, momentary food-reward values, complex flavors and odors. As breathing rhythm has an influence on odor processing at primary olfactory areas, we tested the hypothesis that it may also influence neuronal activity in the OFC, a prefrontal area involved also in higher order processing of odors. We recorded spike timing of orbitofrontal neurons as well as local field potentials (LFPs) in awake, head-fixed mice, together with the breathing rhythm. We observed that a large majority of orbitofrontal neurons showed robust phase-coupling to breathing during immobility and running. The phase coupling of action potentials to breathing was significantly stronger in orbitofrontal neurons compared to cells in the medial prefrontal cortex. The characteristic synchronization of orbitofrontal neurons with breathing might provide a temporal framework for multi-variable processing of olfactory, gustatory and reward-value relationships. [ABSTRACT FROM AUTHOR]